P742: THE VALUE OF S100A8 AND S100A9 FOR DIAGNOSIS AND PROGNOSTIC PREDICTION IN MYELODYSPLASTIC NEOPLASMS
Authors: Xuefeng LI, Yu Wu
Journal: HemaSphere (2023)

Background: myelodysplastic neoplasms (MDS) are a group of heterogeneous neoplasms originating from bone marrow (BM) hematopoietic stem cells. S100A8 and S100A9 are molecules involved in various pathogenetic pathways of MDS, but they lack comprehensive analysis by the combination of molecule concentrations with clinical data. Aims: Our study measured the S100A8 and S100A9 concentrations in BM supernatant from patients with MDS or acquired aplastic anemia (AA), analyzed the correlation between clinical data and the concentrations, and aimed to explore the value of those molecules for the differential diagnosis and prognostic prediction of MDS. Methods: We used BM aspiration to collect BM fluid from patients newly diagnosed with MDS (n=80) or AA (n=26) from June 2021 to November 2022. The BM supernatant was isolated and extracted by centrifuge set to 3000 rpm/10 minutes. The concentrations of S100A8 and S100A9 in BM supernatant were measured using enzyme-linked immunosorbent assay (ELISA). We also analyzed the factors which might influence the concentrations of these molecules. A P<0.05 was considered statistically significant. Results: Our study found the concentrations of S100A8 and S100A9 in the BM supernatant of MDS were both significantly higher than those of AA (Figure 1 and 2, Both P<0.05). Subgroup analysis also showed that lower-risk MDS [Very low and low by IPSS-R (Age-adjusted)] had higher concentrations of the two molecules than AA patients (Both P<0.05). The diagnostic test showed that S100A8 and S100A9 had values for differential diagnosis between lower-risk MDS and AA (Both AUC>0.7); the parallel diagnostic test of these two molecules resulted in a high negative predictive value (NPV=0.842). Our study also found that the concentrations of S100A8 and S100A9 in MDS patients were significantly positively correlated with the patient’s age, and the proportion of granulocytes in the BM (Both P<0.05). Meanwhile, the concentrations of the two molecules had significantly negative correlations with the proportions of erythroid and lymphoid cells in the BM (Both P<0.05). When excluding outliers, the simple linear regression showed that the concentration of S100A8 rose slightly by the increased proportion of BM blasts (Figure 3, P=0.188); while S100A9 gradually decreased (Figure 4, P=0.081). Besides, S100A8 had a significantly positive correlation with STAG2 mutation (P<0.05). However, their concentrations did not show significant differences by risk stratification (Figure 5 and 6; either by IPSS-RA or IPSS-M, P>0.05). Summary/Conclusion: The concentrations of S100A8 and S100A9 in the BM supernatant of MDS have values for differential diagnosis between MDS and AA. The parallel diagnostic test of these two molecules could be helpful to exclude the possibility of diagnosing lower-risk MDS. The correlations of the two molecules with age, proportions of BM lineages and etc., reflected the therapeutic values of targeting S100A8 and S100A9 for MDS patients with different clinical features. S100A8 and S100A9 might play different or even opposite roles in the transformation of MDS to AML; but they lacked prognostic values in MDS due to insignificant differences by IPSS-RA or IPSS-M.Keywords: Diagnosis, Aplastic anemia, Myelodysplastic syndrome, Prognosis